MA (Cantab) MBBS PhD FRCP (Lond)
Professor of Clinical Neurology & Neuroscience
- Consultant Neurologist, John Radcliffe Hospital
Biomarker development in MND/ALS
My group's research involves patients diagnosed with motor neurone disease (MND), known in its commonest form as amyotrophic lateral sclerosis (ALS).
MND is a progressive neurodegenerative disease that dramatically shortens the lives of the majority of those who develop it because there is no effective disease-modifying treatment as yet. It causes relentless weakness in the limbs and often speech and swallowing muscles, with loss of independence and eventual respiratory failure. Those who develop MND have typically led healthy, active lives, and only a minority have a family history of the disease or the related condition frontotemporal dementia (FTD).
My group is trying to identify markers of disease activity across the different types of MND. These are called biomarkers. There is no test for MND, so diagnosis relies on the opinion of an expert neurologist, and any investigations are currently only to exclude other possible causes for the same symptoms (of which there are not many). Biomarkers might be able to shorten the delay of up to one year that many patients with MND have to wait to get a firm diagnosis. This might allow potential therapies to be introduced earlier, before there is spread of symptoms to more than one body region. It would also allow drug trials to be organised more efficiently, by categorizing patients according to disease activity, and making decisions about efficacy much sooner.
The Oxford Study for Biomarkers in MND ('BioMOx') is a platform for studying MND patient volunteers (of all different sub-types) who have agreed to undergo advanced magnetic resonance imaging (MRI) and magnetoencephalographic (MEG) studies of the brain along with spinal fluid and blood samples, to define potential biomarkers. We are also keen to study healthy volunteers and individuals with conditions that look similar to MND for comparison.
BioMOx has already identified a series of potential changes in the brains of MND patients that might be able to serve as biomarkers when combined together, and with substances identified in the blood and spinal fluid samples.
A new initiative: Families for the Treatment of Hereditary MND, FaTHoM, includes the study of rare individuals from families where members of successive generations develop MND, or sometimes FTD. This will allow us to identify the very earliest changes, and ways to intervene and prevent MND and FTD, with the aim of translating these findings to those already living with the disease.
Find out more at: www.biomox.net
Aside from my research, as a consultant neurologist at the John Radcliffe Hospital I see patients with a range of other neurological diseases in my outpatient clinic, and contribute to the acute out-of-hours service. I chair the Association of British Neurologists Research Committee with oversight of their flagship Clinical Research Training Fellowship scheme. I am Senior Research Fellow at Green Templeton College, and undertake regular teaching of Oxford University medical students, as well as educating junior doctors and regional GPs about all aspects of neurological disease.
Revised Airlie House consensus guidelines for design and implementation of ALS clinical trials.
van den Berg LH. et al, (2019), Neurology
Transcriptome Analysis of Infected and Bystander Type 2 Alveolar Epithelial Cells during Influenza A Virus Infection Reveals In Vivo Wnt Pathway Downregulation.
Hancock AS. et al, (2018), J Virol, 92
ALS-associated missense and nonsense TBK1 mutations can both cause loss of kinase function.
de Majo M. et al, (2018), Neurobiol Aging, 71, 266.e1 - 266.e10
The reunification of amyotrophic lateral sclerosis.
Turner MR., (2018), J Neurol Neurosurg Psychiatry
Towards a TDP-43-Based Biomarker for ALS and FTLD.
Feneberg E. et al, (2018), Mol Neurobiol, 55, 7789 - 7801